Angiogenesis

, Volume 3, Issue 1, pp 9–14 | Cite as

Angiogenesis and ophthalmic disease

  • Anthony P. Adamis
  • Lloyd P. Aiello
  • Robert A. D'Amato
Article

Abstract

Ocular angiogenesis is responsible for the majority of irreversible blindness in the developed world [1]. This debilitating complication affects all age groups and characterizes such diverse and widespread diseases as trachoma, retinopathy of prematurity, diabetic retinopathy, neovascular glaucoma and age-related macular degeneration. Although numerous relatively rare conditions also exhibit ocular angiogenesis, the aim of this review will be to briefly summarize our current knowledge regarding the clinical and laboratory findings of the most epidemiologically significant diseases. We will also describe current concepts regarding the pathogenesis of ocular angiogenesis. In this review the term ‘neovascularization’, which is more prevalent in the ophthalmic literature, will be used to describe the development of pathological new vessels and should be considered synonymous with ‘angiogenesis’.

angiogenesis choroid cornea development eye iris neovascularization 

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References

  1. 1.
    Lee P, Wang CC, Adamis AP. Ocular neovascularization: An epidemiological review. Surv Ophthalmol 1998; 43: 245–69.PubMedCrossRefGoogle Scholar
  2. 2.
    Huang AJW, Watson BD, Hernandez E, Tseng SCG. Induction of conjunctival transdifferentiation on vascularized corneas by photothrombotic occlusion of corneal neovascularization. Ophthalmology 1988; 95: 228–35.PubMedGoogle Scholar
  3. 3.
    Huang AJW, Watson BD, Hernandez E, Tseng SCG. Induction of conjunctival transdifferentiation on vascularized corneas by photothrombotic occlusion of corneal neovascularization. Ophthalmology 1988; 95: 228–35.PubMedGoogle Scholar
  4. 4.
    Arentsen JJ. Corneal neovascularization in contact lens wearers. Int Ophthalmol Clin 1986; 26: 15–23.PubMedGoogle Scholar
  5. 5.
    Kruse FE, Chen JJY, Tsai RJF, Tseng SCG. Conjunctival transdifferentiation is due to the incomplete removal of limbal basal epithelium. Invest Ophthalmol Vis Sci 1990; 31: 1903–13.PubMedGoogle Scholar
  6. 6.
    Klintworth GK. Corneal Angiogenesis. A Comprehensive and Critical Review, 1st edition. New York: Springer-Verlag 1990; 26.Google Scholar
  7. 7.
    Amano S, Rohan R, Kuroki M et al. Requirement for vascular endothelial growth factor in wound-and inflammation-related corneal neovascularization. Invest Ophthalmol Vis Sci 1998; 39: 18–22.PubMedGoogle Scholar
  8. 8.
    Cursifen C, Hofman-Rummelt C, Kuche MNGOH. VEGF-immunoreactivity in human corneal buttons with neovascularization. ARVO abstracts. Invest Ophthalmol Vis Sci 1998; 39: S3418.Google Scholar
  9. 9.
    Michaelson IC. The mode of development of the vascular system of the retina, with some observations on its significance for certain retinal disease. Trans Ophthalmol Soc UK 1948; 68: 137–80.Google Scholar
  10. 10.
    Ashton N. Retinal vascularization in health and disease. Am J Ophthlamol 1957; 44: 7–24.Google Scholar
  11. 11.
    Wise GN. Retinal neovascularization. Trans Am Ophthalmol Soc 1956; 54: 729–826.PubMedGoogle Scholar
  12. 12.
    Nork TM, Tso MO, Duvall J, Hayreh SS. Cellular mechanisms of iris neovascularization secondary to retinal vein occlusion. Arch Ophthalmol 1989; 107: 581–6.PubMedGoogle Scholar
  13. 13.
    Schultze RR. Rubeosis iridis. Am J Ophthalmol 1967; 63: 487–95.Google Scholar
  14. 14.
    Shima DT, Gougos A, Miller JW et al. Cloning and mRNA expression of VEGF in ischemic retinas of Maccaca fasicularis. Invest Ophthalmol Vis Sci 1996; 37: 1334–40.PubMedGoogle Scholar
  15. 15.
    Miller J, Adamis AP, Shima DT et al. Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol 1994; 145: 574–84.PubMedGoogle Scholar
  16. 16.
    Adamis AP, Shima DT, Tolentino M et al. Inhibition of VEGF prevents retinal ischemia-associated iris neovascularization in a primate. Arch Ophthalmol 1996; 114: 66–71.PubMedGoogle Scholar
  17. 17.
    Tolentino MJ, Miller JW, Gragoudas ES et al. Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate. Arch Ophthalmol 1996; 114: 964–70.PubMedGoogle Scholar
  18. 18.
    Pe'er J, Shweiki D, Itin A et al. Hypoxia-induced expression of vascular endothelial growth factor by retinal cells is a common factor in neovascularizing ocular diseases. Lab Invest 1995; 72: 638–45.PubMedGoogle Scholar
  19. 19.
    Aiello LP, Avery RL, Arrigg PG et al. Vascular endothelial growth factor in ocular fluid of patients wth diabetic retinopathy and other retinal disorders. N Engl J Med 1994; 331: 1480–87.PubMedCrossRefGoogle Scholar
  20. 20.
    Pournaras CJ, Tsacopoulos M, Strommer K et al. Scatter photocoagulation restores tissue hypoxia in experimental vasoproliferative microangiopathy in miniature pigs. Ophthalmology 1990; 97: 1329–33.PubMedGoogle Scholar
  21. 21.
    Pournaras CJ, Miller JW, Gragoudas ES et al. Systemic hyperoxia decreases vascular endothelial growth factor gene expression in ischemic primate retina. Arch Ophthalmol 1997; 115: 1553–8.PubMedGoogle Scholar
  22. 22.
    Imesch PD, Bindley CD, Wallow IH. Clinicopathologic correlation of intraretinal microvascular abnormalities. Retina 1997; 17: 321–9.PubMedGoogle Scholar
  23. 23.
    Tolentino MJ, Miller JW, Gragoudas ES et al. Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. Ophthalmology 1996; 103: 1820–8.PubMedGoogle Scholar
  24. 24.
    The Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: The second report of the diabetic retinopathy study findings. Ophthalmology 1978; 85: 82–92.Google Scholar
  25. 25.
    Federman JL, Boyer D, Lanning R, Breit P. An objective analysis of proliferative diabetic retinopathy before and after pars plana vitrectomy. Ophthalmology 1979; 86: 276–82.PubMedGoogle Scholar
  26. 26.
    Schroder S, Palinski, Schmid-Schonbein GW. Activated monocytes and granulocytes, capillary non-perfusion, and neovascularization in diabetic retinopathy. Am J Pathol 1991; 139: 81–00.PubMedGoogle Scholar
  27. 27.
    McLeod DS, Lefer DJ, Merges C, Lutty GA. Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid. Am J Pathol 1995; 147: 642–53.PubMedGoogle Scholar
  28. 28.
    Miyamoto K, Ogura Y. Role of leukocytes in diabetic microcirculatory disturbances. Microvas Res 1997; 54: 43–8.CrossRefGoogle Scholar
  29. 29.
    Braun RD, Fisher TC, Meiselman HJ, Hatchell DL. Decreased deformability of polymorphonuclear leukocytes in diabetic cats. Microcirculation 1996; 3: 271–8.PubMedGoogle Scholar
  30. 30.
    Kelly LW, Barden CA, Tiedeman JS, Hatchell DL. Alterations in viscosity and filterability of whole blood and blood cell subpopulations in diabetic cats. Exp Eye Res 1993; 56: 341–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Dobbie JG, Kwaan HC, Colwell J, Suwanwela N. Role of platelets in pathogenesis of diabetic retinopathy. Arch Ophthalmol 1974; 91: 107–9.PubMedGoogle Scholar
  32. 32.
    Diacovo TG, Puri KD, Warnock RA et al. Platelet-mediated lymphocyte delivery to high endothelial venules. Science 1996; 273: 252–5.PubMedGoogle Scholar
  33. 33.
    Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992; 359: 843–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Aiello LP, Northrup JM, Keyt BA et al. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Archives of Ophthalmology 1995; 113: 1538–44.PubMedGoogle Scholar
  35. 35.
    Takagi H, King GL, Robinson GS et al. Adenosine mediates hypoxic induction of vascular endothelial growth factor in retinal pericytes and endothelial cells. Invest Opthalmol Vis Sci 1996; 37: 2165–76.Google Scholar
  36. 36.
    Xia P, Aiello LP, Ishii H et al. Characterization of vascular endothelial growth factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. J Clin Invest 1996; 98: 2018–26.PubMedGoogle Scholar
  37. 37.
    Thieme H, Aiello LP, Takagi H et al. Comparative analysis of vascular endothelial growth factor receptors on retinal and aortic vascular endothelial cells. Diabetes 1995; 44: 98–103.PubMedGoogle Scholar
  38. 38.
    Okamoto N, Tobe T, Hacket SF et al. Transgenic mice with increased expression of vascular endothelial growth factor in the retina. A new model of intraretinal and subretinal neovascularization. Am J Pathol 1997; 151: 281–91.PubMedGoogle Scholar
  39. 39.
    Aiello LP, Pierce EA, Foley ED et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci USA 1995; 92: 10457–61.PubMedCrossRefGoogle Scholar
  40. 40.
    Takagi H, King GL, Aiello LP. Identification and characterization of vascular endothelial growth factor receptor (Flt) in bovine retinal pericytes. Diabetes 1996; 45: 1016–23.PubMedGoogle Scholar
  41. 41.
    Adamis AP, Miller J, Bernal M-T et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 1994; 118: 445–50.PubMedGoogle Scholar
  42. 42.
    Shima D, Adamis AP, Ferrara N et al. Hypoxic induction of endothelial cell growth factors in retinal cells: Identification and characterization of vascular endothelial growth factor (VEGF) as the mitogen. Mol Med 1995; 2: 182–93.Google Scholar
  43. 43.
    Malecaze F, Clamens S, Simorre-Pinatel V et al. Detection of vascular endothelial growth factor messanger RNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol 1994; 112: 1476–82.PubMedGoogle Scholar
  44. 44.
    Hata Y, Duh E, Zhang K et al. Transcriptoin factors sp1 and sp3 affect vascular endothelial growth factor receptor KDR expression through a novel recognition sequence. J Biol Chem 1998; 273: 19294–303.PubMedCrossRefGoogle Scholar
  45. 45.
    Ishii H, Jirousek MR, Koya D et al. Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science 1996; 272: 728–31.PubMedGoogle Scholar
  46. 46.
    Danis RP, Bingaman DP, Jirousek M, Yang Y. Inhibition of intraocular neovascularizatoin caused by retinal ischemia in pigs by PKCbeta inhibition with LY333531. Invest Ophthalmol Vis Sci 1998; 39: 171–9.PubMedGoogle Scholar
  47. 47.
    Aiello LP, Bursell SE, Clermont A et al. Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes 1997; 46: 1473–80.PubMedGoogle Scholar
  48. 48.
    Hammes H-P, Brownlee M, Jonczyk A et al. Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization. Nature Med 1996; 2: 529–33.PubMedCrossRefGoogle Scholar
  49. 49.
    Luna J, Tobe T, Mousa SA et al. Antagonists of integrin alpha v beta 3 inhibit retinal neovascularization in a murine model. Lab Invest 1998; 75: 563–73.Google Scholar
  50. 50.
    Friedlander M, Brooks PC, Shaffer RW et al. Definition of two angiogenic pathways by distinct alpha v integrins. Science 1995; 270: 1500–2.PubMedGoogle Scholar
  51. 51.
    Smith LE, Kopchick JJ, Chen W et al. Essential role of growth hormone in ischemia-induced retinal neovascularization. Science 1997; 276: 1706–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Freund KB, Yannuzzi LA, Sorenson JA. Age-related macular degeneration of choroidal neovascularization. Am J Ophthalmol 1993; 115: 786–91.PubMedGoogle Scholar
  53. 53.
    Group MPS. Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Arch Ophthalmol 1990; 108: 825–31.Google Scholar
  54. 54.
    Sarks SH. Ageing and degeneration in the macular region: A clinico-pathological study. Br J Ophthalmol 1976; 60: 324–41.PubMedGoogle Scholar
  55. 55.
    Chen JC, Fitzke FW, Pauleikhoff D, Bird AC. Functional loss in age-related Bruch's membrane change with choroidal perfusion defect. Invest Ophthalmol Vis Sci 1992; 33: 334–40.PubMedGoogle Scholar
  56. 56.
    Green WR, Enger C. Age-related macular degeneration histopathological studies. Ophthalmology 1992; 100: 1519–35.Google Scholar
  57. 57.
    Bressler NM, Bressler SB, Fine SL. Age-related macular degeneration. [Review]. Surv Ophthalmol 1988; 32: 375–413.PubMedCrossRefGoogle Scholar
  58. 58.
    Allikmets R, Shroyer NF, Singh N et al. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science 1997; 277: 1805–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Lopez PF, Sippy BD, Lambert HM et al. Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes. Invest Ophthalmol Vis Sci 1996; 37: 855–68.PubMedGoogle Scholar
  60. 60.
    Ishibashi T, Hata Y, Yoshikawa H et al. Expression of vascular endothelial growth factor in experimental choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol 1997; 235: 159–67.PubMedCrossRefGoogle Scholar
  61. 61.
    Friedlander M, Brooks PC, Shaffer RW et al. Definition of two angiogenic pathways by distinct alpha v integrins. Science 1995; 270: 1500–2.PubMedGoogle Scholar
  62. 62.
    Ferrara N, Carver-Moore K, Chen H et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996; 380: 439–42.PubMedCrossRefGoogle Scholar
  63. 63.
    Stone J, Itin A, Alon T et al. Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J Neurosci 1995; 15: 4738–47.PubMedGoogle Scholar
  64. 64.
    Zhang Y, Stone J. Role of astrocytes in the control of developing retinal vessels. Invest Ophthalmol Vis Sci 1997; 38: 1653–66.PubMedGoogle Scholar
  65. 65.
    Benjamin LE, Hemo I, Keshet E. A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 1998; 125: 1591–8.PubMedGoogle Scholar
  66. 66.
    Alon T, Hemo I, Itin A et al. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nature Med 1995; 1: 1024–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Benjamin LE, Golijanin D, Itin A et al. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 1999; 103: 159–65.PubMedCrossRefGoogle Scholar
  68. 68.
    Williamson JR, Chang K, LeJeune W et al. Links between retinal vascular dysfunction induced by elevated glucose levels and VEGF. ARVO abstracts. Invest Ophthalmol Vis Sci 1996; 37: S47.Google Scholar
  69. 69.
    Miyamoto K, Ogura Y, Hamada M et al. In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 1996; 37: 2708–15.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Anthony P. Adamis
    • 1
    • 2
  • Lloyd P. Aiello
    • 3
  • Robert A. D'Amato
    • 1
    • 2
  1. 1.Massachusetts Eye and Ear InfirmaryBostonUSA
  2. 2.Children's HospitalBostonUSA
  3. 3.Beetham Eye Institute, Joslin Diabetes Center, Department of OphthalmologyHarvard Medical SchoolBostonUSA

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